Williams Brendan M, Tamaoki Yuko, Danaphongse Tanya T, Myers Isabella K, Kroon Samantha L, Solano Maria P, Jacob Allan A, Riley Jonathan R, Chen Min, Hays Seth A, Engineer Crystal T
Department of Neuroscience, School of Behavioral and Brain Sciences, The University of Texas at Dallas, Richardson, TX, United States.
Texas Biomedical Device Center, The University of Texas at Dallas, Richardson, TX, United States.
Front Neurosci. 2025 Jun 13;19:1600024. doi: 10.3389/fnins.2025.1600024. eCollection 2025.
INTRODUCTION: Prenatal exposure to valproic acid (VPA) is a common environmental cause of autism spectrum disorder (ASD) and often leads to expressive and receptive language impairments. Similar communication difficulties among individuals with ASD are often linked to abnormal subcortical and cortical sound processing. Rodents prenatally exposed to VPA exhibit degraded cortical responses to speech and an impaired ability to behaviorally discriminate speech sounds. METHODS: We sought to determine whether sound processing could be restored with paired vagus nerve stimulation (VNS). In a first experiment, we evaluated whether sound-paired VNS would alter extracellular multi-unit responses to tones, noise burst trains, and speech sounds from the anterior auditory field. We next sought to evaluate whether improvements to neural sound processing led to improvements in sound discrimination ability. In a second experiment, rats underwent go/no-go sound discrimination testing where VNS was paired with successful trials. RESULTS: We found that VPA-exposed rats had degraded spectral, temporal, and speech sound processing compared to saline-exposed control rats. VPA-exposed rats which received sound-paired VNS exhibited a partial or full restoration of processing across sound types. However, across several sound discrimination tasks, we did not observe changes in behavioral performance in response to prenatal exposure to VPA or VNS. DISCUSSION: Our study is the first to show that speech-paired VNS leads to a generalized improvement in cortical sound processing across sound types, rescuing neural processing among VPA-exposed rats. These results provide a framework for future studies to develop VNS-based interventions for communication disorders.
引言:产前接触丙戊酸(VPA)是自闭症谱系障碍(ASD)常见的环境致病因素,常导致表达性和接受性语言障碍。ASD患者中类似的沟通困难通常与皮层下和皮层声音处理异常有关。产前接触VPA的啮齿动物对语音的皮层反应退化,行为上区分语音的能力受损。 方法:我们试图确定配对迷走神经刺激(VNS)是否能恢复声音处理能力。在第一个实验中,我们评估声音配对的VNS是否会改变来自前听觉场的音调、噪声爆发序列和语音的细胞外多单元反应。接下来,我们试图评估神经声音处理的改善是否会导致声音辨别能力的提高。在第二个实验中,大鼠接受了“去/不去”声音辨别测试,其中VNS与成功试验配对。 结果:我们发现,与生理盐水处理的对照大鼠相比,接触VPA的大鼠的频谱、时间和语音处理能力退化。接受声音配对VNS的VPA暴露大鼠在各种声音类型的处理上表现出部分或完全恢复。然而,在几个声音辨别任务中,我们没有观察到产前接触VPA或VNS对行为表现的影响。 讨论:我们的研究首次表明,语音配对的VNS能使各种声音类型的皮层声音处理得到普遍改善,挽救VPA暴露大鼠的神经处理能力。这些结果为未来研究开发基于VNS的沟通障碍干预措施提供了框架。
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